We have developed an experimental model in which to study pulmonary edema development after myocardial ischemia (MI). We shall use anesthetized sheep objected to coronary artery ligation or coronary microembolization. Prior to induction of MI we will establish controlled moderate, steady-state elevations of left atrial pressure using an in situ balloon. The efferent duct of the caudal mediastinal lymph node and a single cardiac lymphatic are cannulated to permit concommitant collections of pulmonary lymph, cardiac lymph and plasma before and after MI or sham MI. We shall determine if we can (a) accentuate edema development after acute MI by (1) pharmacologic alterations of the balance of circulating endogenous prostaglandins and (2) decreased catabolism of endogenous bradykinin and if we can (b) limit deema formation after acute MI by (1) administration of steroidal and non-steroidal anit-inflammatory agents, and (2) administration of a protease inhibitor. In each sample of lymph and plasma we will determine the concentrations of E, F, and I series prostaglandins, thromboxane B(2) and bradykinin. We will also determine the concentration of protein and several protein fractions in each sample. Using gravimetric techniques we will determine the extravascular water content of the lungs and hearts excised from these animals. Results of these experiments will provide new information regarding interrelationships among the kallikrein-kinin system, prostaglandins, and constituents of the clotting system which lead to edema formation in acute MI. Moreover, our results may provide a rationale for specific therapeutic interventions to limit edema formation after acute myocardial ischemia.